Epidemiological studies indicate that the major source of human cancer is of environmental origin and is related to dietary habits. The effect of unsaturated and saturated fats on mouse skin are being assessed by feeding synthetic diets to mice throughout the initiation and promotion process. Groups of 30 mice were initiated with 30mg beta-propiolactone and 25 micrograms DMBA. They were put on diets containing saturated and unsaturated fat at two levels--4% and 15%. All groups were treated 3 times a week with 5mg phorbol myristate acetate as tumor promoter. There was a strikingly greater tumor yield after three months on the polyunsaturated diets. On the 15% fat diet, BPL initiated mice on the unsaturated diet showed 22 tumors, while the animals on saturated fat showed 4 tumors. With the DMBA-initiated the animals on the unsaturated diet showed 122 tumors, on the saturated diets--21. The following tentative conclusions can be drawn from this experiment: 1) Unsaturated fat enhances the action of the tumor promoter PMA. 2) Unsaturated fat has the same effect on DMBA initiation as on PBL; thus, is not involved in the activation of the carcinogen DMBA, which requires activation. 3) The proximal agent of unsaturated fat in this process requires investigation. Possible candidates are Malonaldehyde, Prostaglandins, or Epoxides. Experiments are planned to delineate further the effect of diet on initiation and promotion by using unsaturated fat during initiation switching to saturated during promotion and vice versa. The saturation of skin lipids will be measured.